Since then, several studies have addressed the potential mechanisms underlying the reduction in incretin effect in T2D and, to make a long history short, the hypotheses raised by Juris Meier and Michael Nauck are summarized hereafter.These authors propose that reductions in GIP and GLP-1 secretions do not appear to contribute significantly to the loss of incretin effect and that there is a reduction in the insulinotropic action of GIP (whereas GLP-1 action is relatively well preserved) secondarily to a general impairment in beta-cell function. This evidence concerns the gene GLP1R and type 2 diabetes mellitus.